Sheila Fleming Receives Parkinson’s Research Grant from Department of Defense

A collaboration between Sheila Fleming, Ph.D., and a colleague at Michigan State University to research the effect of exercise in Parkinson’s disease has received major funding from the Department of Defense. The two researchers on this partnering grant will essentially split the funding, which amounts to about $1 million each, said Dr. Fleming, who is an assistant professor of pharmaceutical sciences at Northeast Ohio Medical University.

Dr. Fleming, the Partnering PI on the grant, is working with Initiating PI Caryl Sortwell, Ph.D.  of Michigan State University. “It’s a major award for both of us,” says Dr. Fleming.

As announced by the Office of Research and Sponsored Programs, Dr. Fleming will receive $954,566 from 9/15/2019 – 9/14/2022 from the U.S. Army Medical Research Acquisition Activity for the project titled “Exercise Effects on Synuclein Aggregation, Neuroinflammation, and Neurodegeneration.”

The collaborators will present their Parkinson’s research at the annual meeting of the Society for Neuroscience this fall.

An ongoing collaboration that fit the bill

What are a couple of scientists doing with a Department of Defense grant?

It’s not as unusual as it might sound, explains Dr. Fleming. Each year, the DOD solicits grant proposals on different topics within different diseases. Last year, it was looking for proposals studying exercise mechanisms in Parkinson’s. Dr. Fleming realized that she and Dr. Sortwell would be a natural fit.

Dr. Sortwell has tracked the time course and development of pathological events happening in the brain in a progressive animal model of Parkinson’s disease. Dr. Fleming focuses on the behavioral side, looking at how these pathological events relate to changes in motor and non-motor behaviors. To that end, the team has been looking at the impact of introducing exercise at different time points, as the disease progresses.

Dr. Fleming explains that researchers studying exercise so far have mostly used so-called toxin models, which exclusively target the dopamine system. (Loss of dopamine neurons is a hallmark of Parkinson’s.)

She and Dr. Sortwell are using a newer model called PFF, for pre-formed fibrils. These are synthetic fibrils that are not themselves toxic, but cause a protein called alpha synuclein to mis-fold, re-seed and spread. That’s important, because it’s accumulated alpha synuclein protein that develops into Lewy Bodies – another pathological sign of the disease — in regions throughout the brain.

This newer PFF model, supported by the Michael J. Fox Foundation, is now the “go-to” model, says Dr. Fleming, who recently served on a grant review panel for the Foundation.

Earlier detection

Research suggests that Lewy body pathology progresses from the back of the brain to the front and that early non-motor symptoms such as anxiety, depression and cognitive impairments may be related to this pathology. Dr. Fleming’s research project will look at both motor and non-motor function and determine what symptoms show up early and in what order. Knowing this could help to detect the disease earlier.

The process involves injecting the PFF into the animal model, then observing the points at which motor issues (such as difficulty walking) and non-motor symptoms (anxiety, depression, reduced sense of smell, sleep or cardiovascular issues, and more) take place.

Potential impact

By the time symptoms are pronounced enough that patients visit a clinic, they’ve typically already lost at least 50% of their dopamine neurons, says Dr. Fleming.

“Slowing the progression of the disease could have a huge benefit, especially since patients aren’t usually diagnosed until between 50 and 60 years of age. So, if you could slow it, that could have a potentially huge impact on the quality of life for patients,” she explains.

Northeast Ohio residents award grant funding

Dr. Fleming and NEOMED researcher Christine Crish, Ph.D., also recently received new funding from Northeast Ohio residents Alan and Janice Wollwho have donated $94,313 to support a related project titled “Woll Postdoctoral Fellow and Graduate Fellow project in Neurodegenerative Disease Research.”

For this project, Drs. Fleming and Crish are studying the therapeutic effectiveness of an exercise hormone called irisin in genetic models of Alzheimer and Parkinson diseases. Dr. Fleming will study the therapeutic effectiveness of irisin in Parkinson’s.

Through support from the Alan and Janice Woll Graduate Assistant Fellowship, Katie Bretland, a second-year graduate student in the Integrated Pharmaceutical Medicine program at NEOMED, will conduct research on both the Alzheimer’s and Parkinson’s projects, with mentoring by both Drs. Crish and Fleming.

Read more about the Woll family’s support.